Effect of cocaine on the histaminergic neuron system in the rat brain.

To examine the effect of cocaine on the brain histamine neuron system, histamine levels and histamine N-methyltransferase activity in the rat brain were measured after the administration of cocaine. Moreover, we examined the effect of L-histidine on cocaine-induced wheel-running behavior. The administration of cocaine (20 mg/kg) increased histamine levels and histamine N-methyltransferase activity in the striatum, nucleus accumbens, and amygdala 1 h later. The pretreatment with L-histidine (350 and 700 mg/kg) inhibited the cocaine (20 mg/ kg)-induced increase of wheel-running activity in a dose-dependent manner. These findings suggest that cocaine activates the brain histamine neuron system, which may play the role of inhibiting the cocaine-induced wheel-running behavior.